期刊
MAYO CLINIC PROCEEDINGS
卷 93, 期 3, 页码 307-320出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.mayocp.2017.10.023
关键词
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资金
- Canadian Institutes for Health Research [MOP-86727]
- Brazilian National Council for Scientific and Technological Development [478416/2009-1]
- Calgary Laboratory Services Internal Research Competition [RS10-533]
- German Federal Ministry of Education and Research of Germany
- German Cancer Research Center (Deutsches Krebsforschungszentrum)
- US National Cancer Institute [K07-CA80668, P50-CA159981, R01CA095023]
- National Institutes of Health (NIH)/National Center for Research Resources/General Clinical Research Center [MO1-RR000056]
- US Army Medical Research and Materiel Command [DAMD17-02-1-0669]
- NIH [R01-CA122443, P50-CA136393, P30-CA15083, U01-CA71966, U01-CA69417, R01-CA16056, K07-CA143047, SFB 685]
- Cancer Research UK [C490/A10119, C490/A10123, C490/A16561]
- UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge
- UK National Institute for Health Research Biomedical Research Centres at University College Hospital Womens Health Theme
- Eve Appeal
- Oak Foundation
- Deutsche Forschungsgemeinschaft
- US Army Medical Research and Material Command [DAMD17-01-1-0729]
- Cancer Council Victoria
- Queensland Cancer Fund
- Cancer Council New South Wales
- Cancer Council South Australia
- Cancer Foundation of Western Australia
- Cancer Council Tasmania
- National Health and Medical Research Council of Australia [ID400413, ID400281]
- Peter MacCallum Cancer Foundation
- Ovarian Cancer Australia
- National Health and Medical Research Council [310670, 628903]
- Cancer Institute NSW [12/RIG/1-17, 15/RIG/1-16, 15/TRC/101]
- National Cancer Institute, Bethesda, MD [R01-CA61107]
- Danish Cancer Society, Copenhagen, Denmark [94 222 52]
- Mermaid I project
- American Cancer Society Early Detection Professorship
- National Center for Advancing Translational Sciences [UL1TR000124]
- [01 GB 9401]
- NATIONAL CANCER INSTITUTE [P30CA016056, P30CA015083, R01CA122443, P50CA159981, R01CA160565, K07CA143047, P50CA136393, R01CA095023, K07CA080668, U01CA069417] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000124] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000056] Funding Source: NIH RePORTER
Objective: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. Patients and Methods: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). Results: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively). Conclusion: Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes. (C) 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.
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